HLA and MuSK‐positive myasthenia gravis: A systemic review and meta‐analysis

OBJECTIVES: Myasthenia gravis (MG) represents a spectrum of clinical subtypes with differences in disease mechanisms and treatment response. MG with muscle-specific tyrosine kinase (MuSK) antibodies accounts for 1%-10% of all MG patients. We conducted a meta-analysis to evaluate the association between HLA genes and MuSK-MG susceptibility. SUBJECTS AND METHODS: Studies were searched in Pubmed, EMBASE database and other sources between 2001 and 2018. Genotype, allele and haplotype frequencies of HLA loci in MuSK-MG patients and healthy controls were extracted from each included study. RESULTS: The meta-analysis showed that HLA DQB1*05, DRB1*14 and DRB1*16 were strongly associated with an increased risk of MuSK-MG (P < .0001), whereas HLA DQB*03 was less frequent in MuSK patients compared with healthy controls (P < .05). Haplotype analysis showed that these DQB1 and DRB1 alleles were closely linked, forming both risk (DQ5-DR14, DQ5-DR16, P < .0001) and protective (DQ3-DR4, DQ3-DR11, P < .05) haplotypes. CONCLUSION: The distinct genetic patterns of MuSK-MG indicate that variation in HLA class II genes plays an important role in the pathogenesis of MuSK-MG patients.